DE60018704T2 - Bretyliumhaltige zusammensetzungen und kits und deren verwendung zur vorbeugung und behandlung cardiovaskulärer erkrankungen - Google Patents

Bretyliumhaltige zusammensetzungen und kits und deren verwendung zur vorbeugung und behandlung cardiovaskulärer erkrankungen Download PDF

Info

Publication number: DE60018704T2
Authority: DE; Germany
Prior art keywords: anion; source; mediating; bretylium; bretylium cation
Prior art date: 1999-01-08
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Lifetime

Application number

DE60018704T

Other languages

German (de)

English (en)

Other versions

DE60018704D1 (de

Inventor

Marvin B. Bacaner

Maurice M. Kreevoy

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Bacaner Marvin B Minneapolis

Kreevoy Maurice M Minneapolis

Original Assignee

Bacaner Marvin B Minneapolis

Kreevoy Maurice M Minneapolis

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1999-01-08

Filing date

2000-01-06

Publication date

2006-05-04

2000-01-06 Application filed by Bacaner Marvin B Minneapolis, Kreevoy Maurice M Minneapolis filed Critical Bacaner Marvin B Minneapolis

2005-04-21 Application granted granted Critical

2005-04-21 Publication of DE60018704D1 publication Critical patent/DE60018704D1/de

2006-05-04 Publication of DE60018704T2 publication Critical patent/DE60018704T2/de

2020-01-07 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

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238000011282 treatment Methods 0.000 title claims description 38
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208000024172 Cardiovascular disease Diseases 0.000 title claims description 4
AAQOQKQBGPPFNS-UHFFFAOYSA-N bretylium Chemical compound CC[N+](C)(C)CC1=CC=CC=C1Br AAQOQKQBGPPFNS-UHFFFAOYSA-N 0.000 claims abstract description 253
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 91
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KVWNWTZZBKCOPM-UHFFFAOYSA-M bretylium tosylate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1.CC[N+](C)(C)CC1=CC=CC=C1Br KVWNWTZZBKCOPM-UHFFFAOYSA-M 0.000 claims description 136
238000002360 preparation method Methods 0.000 claims description 115
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SSILHZFTFWOUJR-UHFFFAOYSA-N hexadecane-1-sulfonic acid Chemical compound CCCCCCCCCCCCCCCCS(O)(=O)=O SSILHZFTFWOUJR-UHFFFAOYSA-N 0.000 claims description 7
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MWKFXSUHUHTGQN-UHFFFAOYSA-N decan-1-ol Chemical compound CCCCCCCCCCO MWKFXSUHUHTGQN-UHFFFAOYSA-N 0.000 claims description 6
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CEMAWMOMDPGJMB-UHFFFAOYSA-N (+-)-Oxprenolol Chemical compound CC(C)NCC(O)COC1=CC=CC=C1OCC=C CEMAWMOMDPGJMB-UHFFFAOYSA-N 0.000 claims description 5
HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 claims description 5
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PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical compound C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 claims description 5
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PAZJSJFMUHDSTF-UHFFFAOYSA-N alprenolol Chemical compound CC(C)NCC(O)COC1=CC=CC=C1CC=C PAZJSJFMUHDSTF-UHFFFAOYSA-N 0.000 claims description 5
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KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 claims description 5
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VKMGSWIFEHZQRS-UHFFFAOYSA-N dichloroisoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(Cl)C(Cl)=C1 VKMGSWIFEHZQRS-UHFFFAOYSA-N 0.000 claims description 5
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239000003961 penetration enhancing agent Substances 0.000 description 1
125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
239000002304 perfume Substances 0.000 description 1
210000003516 pericardium Anatomy 0.000 description 1
230000002085 persistent effect Effects 0.000 description 1
239000008024 pharmaceutical diluent Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
210000003800 pharynx Anatomy 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
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239000011591 potassium Substances 0.000 description 1
229960003975 potassium Drugs 0.000 description 1
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229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
235000015497 potassium bicarbonate Nutrition 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
ONQDVAFWWYYXHM-UHFFFAOYSA-M potassium lauryl sulfate Chemical compound [K+].CCCCCCCCCCCCOS([O-])(=O)=O ONQDVAFWWYYXHM-UHFFFAOYSA-M 0.000 description 1
CAKBNQBJZWWLIW-UHFFFAOYSA-M potassium;hexadecane-1-sulfonate Chemical compound [K+].CCCCCCCCCCCCCCCCS([O-])(=O)=O CAKBNQBJZWWLIW-UHFFFAOYSA-M 0.000 description 1
229920003124 powdered cellulose Polymers 0.000 description 1
235000019814 powdered cellulose Nutrition 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
230000008569 process Effects 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
238000012545 processing Methods 0.000 description 1
239000000047 product Substances 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical compound CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 description 1
229950007666 propyromazine Drugs 0.000 description 1
OANVFVBYPNXRLD-UHFFFAOYSA-M propyromazine bromide Chemical compound [Br-].C12=CC=CC=C2SC2=CC=CC=C2N1C(=O)C(C)[N+]1(C)CCCC1 OANVFVBYPNXRLD-UHFFFAOYSA-M 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
150000003254 radicals Chemical group 0.000 description 1
230000029058 respiratory gaseous exchange Effects 0.000 description 1
210000005241 right ventricle Anatomy 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
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239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
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229920006395 saturated elastomer Polymers 0.000 description 1
CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
230000028327 secretion Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
238000007493 shaping process Methods 0.000 description 1
239000004208 shellac Substances 0.000 description 1
ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
229940113147 shellac Drugs 0.000 description 1
235000013874 shellac Nutrition 0.000 description 1
210000000813 small intestine Anatomy 0.000 description 1
229940083542 sodium Drugs 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
239000007901 soft capsule Substances 0.000 description 1
239000008279 sol Substances 0.000 description 1
239000002904 solvent Substances 0.000 description 1
VIDRYROWYFWGSY-UHFFFAOYSA-N sotalol hydrochloride Chemical compound Cl.CC(C)NCC(O)C1=CC=C(NS(C)(=O)=O)C=C1 VIDRYROWYFWGSY-UHFFFAOYSA-N 0.000 description 1
238000002798 spectrophotometry method Methods 0.000 description 1
208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
239000004575 stone Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000001384 succinic acid Chemical class 0.000 description 1
230000001629 suppression Effects 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
230000008961 swelling Effects 0.000 description 1
230000001975 sympathomimetic effect Effects 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000007916 tablet composition Substances 0.000 description 1
239000007885 tablet disintegrant Substances 0.000 description 1
239000011975 tartaric acid Chemical class 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
210000000779 thoracic wall Anatomy 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
230000001052 transient effect Effects 0.000 description 1
230000008733 trauma Effects 0.000 description 1
229940117013 triethanolamine oleate Drugs 0.000 description 1
NACZPBOVCXPUJN-UHFFFAOYSA-N tris-decyl(methyl)azanium Chemical compound CCCCCCCCCC[N+](C)(CCCCCCCCCC)CCCCCCCCCC NACZPBOVCXPUJN-UHFFFAOYSA-N 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
230000002792 vascular Effects 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
239000001993 wax Substances 0.000 description 1
238000009736 wetting Methods 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/485—Inorganic compounds
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Cardiology (AREA)
Chemical Kinetics & Catalysis (AREA)
Organic Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Heart & Thoracic Surgery (AREA)
Epidemiology (AREA)
Inorganic Chemistry (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Hospice & Palliative Care (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

DE60018704T 1999-01-08 2000-01-06 Bretyliumhaltige zusammensetzungen und kits und deren verwendung zur vorbeugung und behandlung cardiovaskulärer erkrankungen Expired - Lifetime DE60018704T2 (de)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
US11514399P	1999-01-08	1999-01-08
US115143P		1999-01-08
US11656799P	1999-01-21	1999-01-21
US116567P		1999-01-21
PCT/US2000/000350 WO2000040232A2 (en)	1999-01-08	2000-01-06	Bretylium compositions and kits, and their use in preventing and treating cardiovascular conditions

Publications (2)

Publication Number	Publication Date
DE60018704D1 DE60018704D1 (de)	2005-04-21
DE60018704T2 true DE60018704T2 (de)	2006-05-04

Family

ID=26812887

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DE60018704T Expired - Lifetime DE60018704T2 (de)	1999-01-08	2000-01-06	Bretyliumhaltige zusammensetzungen und kits und deren verwendung zur vorbeugung und behandlung cardiovaskulärer erkrankungen

Country Status (10)

Country	Link
US (1)	US6482811B1 (ja)
EP (1)	EP1140054B1 (ja)
JP (1)	JP4750278B2 (ja)
AT (1)	ATE290857T1 (ja)
AU (1)	AU781996B2 (ja)
CA (1)	CA2358459C (ja)
DE (1)	DE60018704T2 (ja)
IL (2)	IL144199A0 (ja)
MX (1)	MXPA01007024A (ja)
WO (1)	WO2000040232A2 (ja)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6884792B2 (en) *	1999-01-08	2005-04-26	Marvin B. Bacaner	Bretylium compositions and kits and their use in preventing and treating cardiovascular conditions
US20040019096A1 (en) *	2001-10-23	2004-01-29	Vlassios Andronis	Novel formulations of carvedilol
RU2376994C2 (ru)	2005-07-22	2009-12-27	Дзе Проктер Энд Гэмбл Компани	Составы для снижения риска возникновения вызванной лекарственными средствами аритмии
JP4750499B2 (ja) *	2005-08-01	2011-08-17	日華化学株式会社	イオン性液体並びにそれを用いた抗菌剤及び抗菌性繊維
EP2953627A4 (en) *	2013-02-07	2017-03-29	Research Foundation Of The City University Of New York	NSAIDs DERIVATIVES AND USES THEREOF
ES2989922T3 (es)	2015-09-17	2024-11-28	Ohio State Innovation Foundation	Compuestos de carborano y métodos de uso de los mismos
US10799138B2 (en)	2018-04-05	2020-10-13	University Of Maryland, Baltimore	Method of administering sotalol IV/switch
US11696902B2 (en)	2018-08-14	2023-07-11	AltaThera Pharmaceuticals, LLC	Method of initiating and escalating sotalol hydrochloride dosing
US10512620B1 (en)	2018-08-14	2019-12-24	AltaThera Pharmaceuticals, LLC	Method of initiating and escalating sotalol hydrochloride dosing
US11344518B2 (en)	2018-08-14	2022-05-31	AltaThera Pharmaceuticals LLC	Method of converting atrial fibrillation to normal sinus rhythm and loading oral sotalol in a shortened time frame
US11610660B1 (en)	2021-08-20	2023-03-21	AltaThera Pharmaceuticals LLC	Antiarrhythmic drug dosing methods, medical devices, and systems
CN115515580A (zh) *	2020-03-11	2022-12-23	俄亥俄州国家创新基金会	使用碳硼烷和碳硼烷类似物调节t细胞活化的方法

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3038004A (en)	1958-04-18	1962-06-05	Burroughs Wellcome Co	Quaternary ammonium compounds
US3441649A (en)	1966-08-18	1969-04-29	Univ Minnesota	Suppression of cardiac ventricular fibrillation and cardiac arrhythmias with bretylium tosylate
US3911125A (en)	1973-05-23	1975-10-07	Marvin B Bacaner	Method of treating angina pectoris, coronary insufficiency, and preventing myocardial infarction
US4147768A (en)	1976-09-13	1979-04-03	Interx Research Corporation	Enteric coated digoxin and therapeutic use thereof
US5288498A (en)	1985-05-01	1994-02-22	University Of Utah Research Foundation	Compositions of oral nondissolvable matrixes for transmucosal administration of medicaments
US5288497A (en)	1985-05-01	1994-02-22	The University Of Utah	Compositions of oral dissolvable medicaments
WO1987005505A1 (en) *	1986-03-21	1987-09-24	Eurasiam Laboratories, Inc.	Pharmaceutical compositions
US4849227A (en)	1986-03-21	1989-07-18	Eurasiam Laboratories, Inc.	Pharmaceutical compositions
US5036106A (en)	1989-09-05	1991-07-30	Bacaner Marvin B	Methods for the treatment of disorders of the cardiac vascular system
US5914132A (en)	1993-02-26	1999-06-22	The Procter & Gamble Company	Pharmaceutical dosage form with multiple enteric polymer coatings for colonic delivery
JP3355593B2 (ja)	1994-08-19	2002-12-09	信越化学工業株式会社	固形腸溶製剤の製造方法
US5733575A (en)	1994-10-07	1998-03-31	Bpsi Holdings, Inc.	Enteric film coating compositions, method of coating therewith, and coated forms
JP3149122B2 (ja)	1994-11-07	2001-03-26	信越化学工業株式会社	固形腸溶製剤のコーティング用基剤
US5686106A (en)	1995-05-17	1997-11-11	The Procter & Gamble Company	Pharmaceutical dosage form for colonic delivery
US5980951A (en)	1996-04-10	1999-11-09	Merck & Co., Inc.	Oral coated active drugs

2000
- 2000-01-06 JP JP2000591989A patent/JP4750278B2/ja not_active Expired - Fee Related
- 2000-01-06 AT AT00904237T patent/ATE290857T1/de not_active IP Right Cessation
- 2000-01-06 MX MXPA01007024A patent/MXPA01007024A/es not_active IP Right Cessation
- 2000-01-06 EP EP00904237A patent/EP1140054B1/en not_active Expired - Lifetime
- 2000-01-06 CA CA2358459A patent/CA2358459C/en not_active Expired - Fee Related
- 2000-01-06 AU AU26023/00A patent/AU781996B2/en not_active Ceased
- 2000-01-06 DE DE60018704T patent/DE60018704T2/de not_active Expired - Lifetime
- 2000-01-06 US US09/869,940 patent/US6482811B1/en not_active Expired - Lifetime
- 2000-01-06 IL IL14419900A patent/IL144199A0/xx active IP Right Grant
- 2000-01-06 WO PCT/US2000/000350 patent/WO2000040232A2/en active IP Right Grant
2001
- 2001-07-08 IL IL144199A patent/IL144199A/en not_active IP Right Cessation

Also Published As

Publication number	Publication date
CA2358459C (en)	2011-05-24
EP1140054A2 (en)	2001-10-10
JP2002534379A (ja)	2002-10-15
US6482811B1 (en)	2002-11-19
CA2358459A1 (en)	2000-07-13
EP1140054B1 (en)	2005-03-16
AU781996B2 (en)	2005-06-23
IL144199A0 (en)	2002-05-23
DE60018704D1 (de)	2005-04-21
IL144199A (en)	2006-10-05
JP4750278B2 (ja)	2011-08-17
WO2000040232A2 (en)	2000-07-13
MXPA01007024A (es)	2002-03-27
WO2000040232A3 (en)	2000-11-23
AU2602300A (en)	2000-07-24
ATE290857T1 (de)	2005-04-15

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DE69904079T2 (de)	2003-07-17	Kombinationen von ileumgallensäuretransports inhibitoren und gallensäure sequestriermitteln für kardiovaskuläre indikationen
EP0861081B1 (de)	2002-02-13	Verwendung von epinastin für die behandlung von schmerzen
DE3875931T2 (de)	1993-03-25	Verbesserung des eindringens in die haut durch verwendung von mischungen der freien base mit dem sauren additionssalz von wirkstoffen.
DE69734742T2 (de)	2006-07-27	Arzneizusammensetzungen enthaltend Ascomycinderivate
DE60018704T2 (de)	2006-05-04	Bretyliumhaltige zusammensetzungen und kits und deren verwendung zur vorbeugung und behandlung cardiovaskulärer erkrankungen
DE2523998A1 (de)	1975-12-11	Pharmazeutische zubereitung fuer die behandlung der schizophrenie
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